Multifunctional composite soluble microneedle patch based on "one stone, three birds" strategy for promoting the healing of infectious wounds.
Colloids and surfaces. B, Biointerfaces
The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the "one stone, three birds" strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.
10.1016/j.colsurfb.2024.114049
Bioinspired Wet Adhesive Proanthocyanidins Microneedles for Ocular Wound Healing.
Research (Washington, D.C.)
Microneedles have shown considerable potential in treating ocular diseases, yet enhancing their architecture and functionality to improve therapeutic efficacy poses marked challenges. Here, inspired by the antioxidant strategy of blueberries and the wet adhesive mechanism of clingfish, we construct hierarchical and multifunctional microneedles. These microneedles possess both wet adhesive and antioxidant properties, making them highly effective for ocular wound healing. Constructed using polyacrylic acid--hydroxysuccinimide-based hydrogel with hexagonal structures, these generated microneedles ensure strong adhesion in wet environments. Furthermore, by incorporating proanthocyanidins (pAc) into the tips, the microneedle is imparted with excellent competence to scavenge reactive oxygen species (ROS). In the rat model of ocular alkali burns, the designed microneedle not only exhibited robust adhesion and desirable antioxidant properties in the moist ocular environment but also facilitated sustained drug release and effective treatment. These results suggest that our bioinspired microneedles with multifunctional properties offer substantial advancement over conventional approaches, positioning them as promising candidates for versatile wound healing applications.
10.34133/research.0485
Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds.
Advanced healthcare materials
Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti-inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, dissolvable microneedle arrays (MNAs) carrying rhPRG4 are engineered for the treatment of skin wounds. The in vitro experiments suggest that rhPRG4 modulates the inflammatory function of bone marrow-derived macrophages. Degradable and detachable microneedles are developed from gelatin methacryloyl (GelMA) attach to a dissolvable gelatin backing. The developed MNAs are able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post-injury, while the GelMA microneedles sustain rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full-thickness wounds with impaired healing confirm a decrease in inflammatory biomarkers such as TNF-α and IL-6, and an increase in angiogenesis and collagen deposition. Collectively, these results demonstrate rhPRG4-incorporating MNA is a promising platform in skin wound healing applications.
10.1002/adhm.202302836
Oral mucosal vaccination using integrated fiber microneedles.
Journal of controlled release : official journal of the Controlled Release Society
The oral mucosa is an attractive site for immunization due to its accessibility and ability to elicit local and systemic immune responses. However, evaluating oral mucosal immunogenicity has proven challenging due to the physical barriers and immunological complexity of the oral mucosa. Microneedles can overcome these physical barriers, but previous work has been limited in the scope of microneedle delivery site, geometry, and release kinetics, all of which are expected to affect physiological responses. Here, we develop integrated fiber microneedle devices, an oral dosage form with tunable geometries and material configurations capable of both burst and sustained release to controlled depths in the oral mucosa. Integrated fiber microneedles administered to either the buccal or sublingual mucosa result in seroconversion and antigen-specific interferon-γ secretion in splenocytes. The dynamics and magnitude of the resulting immune response can be modulated by tuning microneedle release kinetics. Optimal microneedle geometry is site-specific, with longer microneedles eliciting greater immunogenicity in the buccal mucosa, and shorter microneedles eliciting greater immunogenicity in the sublingual mucosa. The Th1/Th2 phenotype of the resulting immune response is also dependent on integrated fiber microneedle length. Together, these results establish integrated fiber microneedles as a multifunctional delivery system for the oral mucosa and motivate further exploration using tunable delivery systems to better understand oral mucosal immunity.
10.1016/j.jconrel.2024.01.062
Research Progress of Hydrogel Microneedles in Wound Management.
ACS biomaterials science & engineering
Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.
10.1021/acsbiomaterials.4c00972
Traditional Chinese Medicine Integrated Multifunctional Responsive Core-Shell Microneedles for Dermatosis Treatment.
Research (Washington, D.C.)
Microneedles have demonstrated value in targeted treatment of dermatosis. Current investigation aims to enhance the functions and optimize substance delivery to improve therapeutic effects. Here, we present innovative shell-core microneedles with light-pH dual responsiveness for spatiotemporal sequential release of multiple Chinese herb drugs to treat scleroderma. By using a stepwise template-assisted method, we effectively prepare a hydrogel-based core layer containing polydopamine-MXene (P-MXene) loaded with triptolide (TP), and a shell layer composed of polyvinyl alcohol (PVA) encapsulating paeoniflorin (Pae). P-MXene can adsorb the sparingly soluble TP to ensure its encapsulation efficiency and contribute to the synergistic photothermal effect benefitting from its excellent photothermal conversion ability. Besides, PVA can rapidly dissolve upon microneedle piercing into the skin and quickly release the anti-inflammatory and detoxifying Pae, establishing a favorable low-acid subcutaneous environment. In response to pH changes and near-infrared effects, TP is sustainably released from P-MXene and delivered through the swollen pores of the hydrogel. On the basis of these characteristics, we demonstrate that these microneedles could effectively reduce profibrotic key cytokines interleukin-1β and transforming growth factor-β, thereby reducing collagen deposition and decreasing epidermal thickness, ameliorating skin fibrosis and capillary lesion in scleroderma mouse models. These findings highlight the important clinical potential of these microneedles in the treatment of skin diseases.
10.34133/research.0420
A Multicomponent Microneedle Patch for the Delivery of Meloxicam for Veterinary Applications.
ACS nano
This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. imaging confirms the microneedle patch penetrates the pig's ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.
10.1021/acsnano.4c08072